Areas of Interest
Trypanosomatids are unicellular, flagellated eukaryotes and a
group of nature’s most versatile parasites infecting all kinds
of vertebrates, insects and even plants. Some of these organisms
cause major human diseases such as African sleeping sickness (Trypanosoma
brucei), Leishmaniases (Leishmania spp.), and Chagas’
disease (Trypanosoma cruzi). Worldwide more than 500
million people are at risk to be infected by these parasites,
and together they account for 150,000 reported deaths and more
than 2 million new clinical cases each year (WHO).
Drugs for these diseases are few and toxic, and parasite
resistance is on the rise. Therefore, it becomes increasingly
important to develop new therapeutic strategies.
We are interested in these parasites’ mechanisms of gene
expression and focus on the identification and functional
characterization of essential factors or factor domains in the
hope to find parasite-specific targets. We work with T.
brucei and our projects address aspects which are specific
to this parasite (multifunctional RNA polymerase I
transcription) and characteristics which are shared by this
group of parasites (spliced leader RNA synthesis).
We employ various methods in cell biology, genetics and
biochemistry including conditional gene expression silencing by
RNA interference. Moreover, we have recently developed useful
functional in vitro assay systems and a modified tandem
affinity purification protocol for proteins which is based on a
novel epitope combination. Together these methods are efficient
means to identify and functionally characterize parasite
proteins.
Lab Rotation Projects
Characterize candidate transcription or trans splicing
factors.
This project involves epitope tagging of a candidate factor,
purification of the factor to homogeneity, and a functional
analysis of the factor conducted in vivo and in vitro.
Analyzing transcription termination.
This projects involves the generation and mutation of
constructs for transcription assays to determine the sequence
element which terminates transcription of the parasite’s
(unique) multifunctional RNA polymerase I.
Selected Publications
Takebe, S, WH Witola, B Schimanski, A Günzl and C Ben Mamoun
(2007). Purification of components of the translation elongation
factor complex of Plasmodium falciparum by tandem affinity
purification. Eukaryot Cell, 6, in press
Lee, JH, TN Nguyen, B Schimanski and A Günzl (2007). SL RNA
gene transcription in Trypanosoma brucei requires transcription
factor TFIIH. Eukaryot Cell 6, in press
Günzl, A, L Vanhamme and PJ Myler (2007). Transcription in
trypanosomes: a different means to the end. In Trypanosomes –
After the Genome. Eds. D Barry, J Mottram, R McCulloch and A
Acosta-Serrano. Horizon Press, Pittsburgh, USA, in press
Skovorodkin, I, A Pimenov, I Raykhel, B Schimanski, D
Ammermann and A Günzl (2007). Analysis of -tubulin
minichromosome promoters in the stichotrichous ciliate
Stylonychia lemnae. Eukaryot Cell 6, 28-36
Nguyen, TN, B Schimanski, A Zahn, B Klumpp and A Günzl
(2006). Purification of an eight subunit RNA polymerase I
complex in Trypanosoma brucei. Mol Biochem Parasitol 149, 27-37
Schimanski, B, J Brandenburg, TN Nguyen, MJ Caimano and A
Günzl (2006). A TFIIB-like protein is indispensable for spliced
leader RNA gene transcription in Trypanosoma brucei. Nucleic
Acids Res 34, 1676-1684
Schimanski, B, TN Nguyen and A. Günzl (2005). Highly
efficient tandem affinity purification of trypanosome protein
complexes based on a novel epitope combination. Eukaryot Cell 4,
1942-1950
Schimanski, B, TN Nguyen and A Günzl (2005). Characterization
of a multi-subunit transcription factor complex essential for SL
RNA gene transcription in Trypanosoma brucei. Mol Cell Biol 25,
7303-7313
Palfi, Z, B Schimanski, A Günzl, S Lücke and A Bindereif
(2005). U1 small nuclear RNP from Trypanosoma brucei: a minimal
U1 snRNA with unusual protein components. Nucleic Acids Res 33,
2493-2503
Schimanski, B, G Laufer, L Gontcharova, and A Günzl (2004).
The Trypanosoma brucei spliced leader RNA and rRNA gene
promoters have interchangeable TbSNAP50-binding elements.
Nucleic Acids Res 32, 700-709.
Günzl, A, T Bruderer, G Laufer, B Schimanski, L-C Tu, H-M
Chung, and MG-S Lee (2003). RNA polymerase I transcribes
procyclin genes and variant surface glycoprotein gene expression
sites in Trypanosoma brucei. Eukaryot Cell 2, 542-551.
Schimanski, B, B Klumpp, G Laufer, RJ Marhöfer, P Selzer, and
A Günzl (2003). The second largest subunit of Trypanosoma
brucei’s multifunctional RNA polymerase I has a unique
N-terminal extension domain. Mol Biochem Parasitol 126, 193-200.
Günzl, A (2003). Transcription. In Molecular and Medical
Parasitology. Eds J.Marr, T. Nilsen, and R. Komuniecki. Academic
Press, London, UK, pages 47-65. |
